Harmony Biosciences Reports Positive Topline Data from Phase 3 Study of Pitolisant in Sleep Disorder

Rare Daily Staff

Harmony Biosciences reported topline results from the INTUNE study in patients with idiopathic hypersomnia, a rare and chronic neurological disease that is characterized by excessive daytime sleepiness despite sufficient or even long sleep time.

Pitolisant demonstrated clinically meaningful benefit in patients completing the initial open label phase of the phase 3 study even though the primary outcome for excessive daytime sleepiness (EDS) between pitolisant and placebo did not reach statistical significance in the randomized withdrawal phase.

Idiopathic hypersomnia (IH) is a rare and chronic neurological disease that is characterized by excessive daytime sleepiness despite sufficient or even long sleep time. People living with IH experience significant EDS along with the symptoms of sleep inertia (prolonged difficulty waking up from sleep) and ‘brain fog’ (impaired cognition, attention, and alertness). The cause of IH is unknown, but it is likely due to alterations in areas of the brain that stabilize states of sleep and wakefulness. IH is one of the central disorders of hypersomnolence and, like narcolepsy, is a debilitating sleep disorder that can result in significant disruption in daily functioning. Approximately 80,000 people in the U.S. are believed to be affected by IH, with 40,000 currently having been diagnosed. IH is a condition with high unmet medical need.

“We are very encouraged by the magnitude of the response seen in the initial open-label treatment period, where 83 percent of patients completing this phase responded with an average 9.4 point improvement in the Epworth Sleepiness Scale (ESS),” said Kumar Budur, chief medical officer at Harmony Biosciences. “Equally encouraging is the number of patients, almost 90 percent, electing to continue into the long-term extension study, allowing us to generate additional safety and efficacy data in this patient population. Positive trends in other important outcomes like sleep inertia add to the totality of evidence that pitolisant has a clinical benefit for patients with IH.”

The INTUNE study was a phase 3 placebo-controlled, double-blind, randomized withdrawal study. Approximately 83 percent of patients who completed the 8-week open-label treatment period with pitolisant were responders (as defined by a decrease on the ESS of ≥3 points) and experienced a robust clinical response, with an average ESS change from baseline of – 9.4 points. A positive trend favoring pitolisant was observed during the 4-week double-blind randomized withdrawal period, however no statistically significant difference was observed between pitolisant and placebo groups on ESS, the primary endpoint. Positive trends favoring pitolisant were also observed across additional prespecified endpoints including the Hypersomnia Severity Scale, which approached statistical significance, as well as on the Sleep Inertia Questionnaire. Approximately 88 percent of patients in the study continued into a 12-month long-term extension study, which is ongoing. The safety and tolerability profile of pitolisant in adult patients with idiopathic hypersomnia was consistent with the established safety profile and no new safety signals were observed.

Following a thorough review of the full data set, Harmony said it will work closely with the U.S. Food and Drug Administration to discuss next steps and a path forward for pitolisant in IH.

Pitolisant is marketed as Wakix in the United States for the treatment of EDS or cataplexy in adult patients with narcolepsy.

Photo: Kumar Budur, chief medical officer at Harmony Biosciences